This invention is based upon the discovery by the inventors of the gene associated with Bloom's syndrome ("BS"), the "BLM gene" or "BLM", and a novel protein encoded by this gene. The discovery of the BLM gene and the protein encoded by the gene will have important implications in the diagnosis and treatment of BS, the recognition of carriers of mutations at BLM, and more broadly in the development of new cancer diagnostics and therapeutics.
BS is a rare autosomal recessive trait characterized clinically by growth deficiency, a sun-sensitive telangiectatic erythema of the face, immunodeficiency, and male infertility (German, J. Medicine 72:393-406 (1993)). Somatic cells from persons with BS are characterized by a striking genomic instability, and display an increased frequency of chromosome abnormalities (breaks, gaps and rearrangements) and inter- and intramolecular exchanges, including sister-chromatid exchanges (Ray, J. H. and German, J. (1983) The cytogenetics of the "chromosome-breakage syndromes." In: German J. (ed.) Chromosome mutations and neoplasia. Alan R. Liss, New York, pp. 135-168). The hypermutability of BS cells is responsible for the benign and malignant neoplasms in BS patients that arise at unusually early ages and in excessive numbers (German, 1993, supra).
Complementation analyses have established that a single locus, designated BLM, is mutated in BS (Weksberg, R., et al. Am. J. Hum. Genet. 42:816-824 (1988)). The BLM locus has been assigned to human chromosome 15 (McDaniel, L. D., and Schultz, R. A. Proc. Natl. Acad. Sci. USA 89:7968-7972 (1992)), and regionally mapped to chromosome band 15q26.1 based upon tight linkage to FES by homozygosity mapping (German, J., et al. Proc. Acad. Natl. Sci. USA 91:6669-6673 (1994)). Prior to the present invention, however, the BLM gene had not been identified.